Cancer is currently the second greatest cause of death in the United States behind coronary heart disease. Even though there is trend toward lower death rates from cancer in the U.S., it has been estimated that the annual personal and financial cost of cancer will be $1.62 trillion dollars by 2017. Further, according to the World Health Organization cancer is set to become the leading cause of death world-wide by 2010.
Cancer is an extremely elusive treatment target in that different types of cancer tend to display different biochemical characteristics and even within one type of cancer, the disease can evolve to become refractory to treatments that once were effective against that variety. This makes treatment choices difficult and is a prime reason for the large number of chemotherapeutics currently available to treat the disease as well as for the huge outlay of research dollars, at present approximately $6 billion dollars per year, spent in the effort to find new more efficacious drugs.
One of the more daunting problems is the ability of cancers to develop resistance to previously effective treatment regimes including both chemotherapeutic agents and radiation therapy. It has been postulated that among the causes of resistance several seem to be particularly ubiquitous across a broad spectrum of solid tumor cancers, those being the up-regulation of the Akt/mTOR pathway, which works to prevent chemotherapeutically induced apoptosis of cancer cells, the up-regulation of protein synthesis that can either directly inhibit the activity of a chemotherapeutic or that can develop an efflux pump to efficiently remove the chemotherapeutic from the cancerous cell before it has a chance to have any beneficial effect and activity of HIF-1α concurrent with the up-regulation of VEGF, which has the effect of stimulating angiogenesis and endothelial cell proliferation in the tumor.
What is needed is a means of inhibiting up-regulation of the Akt/mTOR pathway and/or the up-regulation of direct drug resistance or the development of efflux pump capability in the cancerous cells and/or inhibition of HIF-1α and VEGF. The current invention provides such a means.